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Impressionen zur Geschichte des Historischen Instituts der Universität des Saarlandes in den 60er Jahren
Early or late initiation of dabigatran versus vitamin-K-antagonists in acute ischemic stroke or TIA: The PRODAST study
Background:
The optimal timing of initiating or resuming anticoagulation after acute ischemic stroke (AIS) or transient ischemic attack (TIA) in patients with atrial fibrillation (AF) is debated. Dabigatran, a non-vitamin K oral anticoagulant (NOAC), has shown superiority against vitamin K antagonists (VKA) regarding hemorrhagic complications.
Aims:
In this registry study, we investigated the initiation of dabigatran in the early phase after AIS or TIA.
Methods:
PRODAST (Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA) is a prospective, multicenter, observational, post-authorization safety study. We recruited 10,039 patients at 86 German stroke units between July 2015 and November 2020. A total of 3,312 patients were treated with dabigatran or VKA and were eligible for the analysis that investigates risks for major hemorrhagic events within 3 months after early (⩽ 7 days) or late (> 7 days) initiation of dabigatran or VKA initiated at any time. Further endpoints were recurrent stroke, ischemic stroke, TIA, systemic embolism, myocardial infarction, death, and a composite endpoint of stroke, systemic embolism, life-threatening bleeding and death.
Results:
Major bleeding event rates per 10,000 treatment days ranged from 1.9 for late administered dabigatran to 4.9 for VKA. Early or late initiation of dabigatran was associated with a lower hazard for major hemorrhages as compared to VKA use. The difference was pronounced for intracranial hemorrhages with an adjusted hazard ratio (HR) of 0.47 (95% confidence interval (CI): 0.10–2.21) for early dabigatran use versus VKA use and an adjusted HR of 0.09 (95% CI: 0.00–13.11) for late dabigatran use versus VKA use. No differences were found between early initiation of dabigatran versus VKA use regarding ischemic endpoints.
Conclusions:
The early application of dabigatran appears to be safer than VKA administered at any time point with regards to the risk of hemorrhagic complications and in particular for intracranial hemorrhage. This result, however, must be interpreted with caution in view of the low precision of the estimate
Evaluation of Preprocessing Methods on Independent Medical Hyperspectral Databases to Improve Analysis
Currently, one of the most common causes of death worldwide is cancer. The development of innovative methods to support the early and accurate detection of cancers is required to increase the recovery rate of patients. Several studies have shown that medical Hyperspectral Imaging (HSI) combined with artificial intelligence algorithms is a powerful tool for cancer detection. Various preprocessing methods are commonly applied to hyperspectral data to improve the performance of the algorithms. However, there is currently no standard for these methods, and no studies have compared them so far in the medical field. In this work, we evaluated different combinations of preprocessing steps, including spatial and spectral smoothing, Min-Max scaling, Standard Normal Variate normalization, and a median spatial smoothing technique, with the goal of improving tumor detection in three different HSI databases concerning colorectal, esophagogastric, and brain cancers. Two machine learning and deep learning models were used to perform the pixel-wise classification. The results showed that the choice of preprocessing method affects the performance of tumor identification. The method that showed slightly better results with respect to identifing colorectal tumors was Median Filter preprocessing (0.94 of area under the curve). On the other hand, esophagogastric and brain tumors were more accurately identified using Min-Max scaling preprocessing (0.93 and 0.92 of area under the curve, respectively). However, it is observed that the Median Filter method smooths sharp spectral features, resulting in high variability in the classification performance. Therefore, based on these results, obtained with different databases acquired by different HSI instrumentation, the most relevant preprocessing technique identified in this work is Min-Max scaling
Label-Free Imaging Analysis of Patient-Derived Cholangiocarcinoma Organoids after Sorafenib Treatment
Monitoring tumor growth dynamics is crucial for understanding cancer. To establish an
in vitro method for the continuous assessment of patient-specific tumor growth, tumor organoids
were generated from patients with intrahepatic CCA (iCCA). Organoid growth was monitored for
48 h by label-free live brightfield imaging. Growth kinetics were calculated and validated by MTS
assay as well as immunohistochemistry of Ki67 to determine proliferation rates. We exposed iCCA
organoids (iCCAOs) and non-tumor intrahepatic cholangiocyte organoids (ICOs) to sub-therapeutic
concentrations of sorafenib. Monitoring the expansion rate of iCCAOs and ICOs revealed that
iCCAO growth was inhibited by sorafenib in a time- and dose-dependent fashion, while ICOs were
unaffected. Quantification of the proliferation marker Ki67 confirmed inhibition of iCCAO growth by
roughly 50% after 48 h of treatment with 4 M sorafenib. We established a robust analysis pipeline
combining brightfield microscopy and a straightforward image processing approach for the labelfree
growth monitoring of patient-derived iCCAOs. Combined with bioanalytical validation, this
approach is suitable for a fast and efficient high-throughput drug screening in tumor organoids to
develop patient-specific systemic treatment options
Potential- und Gefährdungsbeurteilung zur Erfassung und Beurteilung von Wohlbefinden und psychischen Gefährdungen unter dreijähriger Kinder in Kindertageseinrichtungen - Handreichung
The Influence of Coordinative Skills on the Oral Health of Children and Adolescents in Permanent Dentition
Removing dental plaque by using a toothbrush is the most important measure for oral
hygiene. The aim of the present study was to estimate the impact of the coordination skills of children and adolescents on their oral health (plaque level, DMF/T: decayed, missing, filled teeth). Within a prospective cohort study, 996 children (10 to 18 years) were examined. The results of three coordination tests from the Motorik Modul (MoMo) were included to evaluate the coordination skills. Other parameters taken into account were age, sex, orthodontic treatment and socioeconomic status (SES). Univariate and various multivariate analyses were performed to evaluate relationships. Better results in precision coordination tests were significantly related to a better oral hygiene (backward
balancing: logistic regression OR 0.86, 95%CI: 0.73–0.99, p = 0.051, proportional odds model OR 0.86, 95%CI: 0.75–0.99, p = 0.037; one-leg-stand: logistic regression OR 0.78, 95%CI: 0.63–0.96, p = 0.018, proportional odds model OR 0.77, 95%CI: 0.64–0.92, p = 0.003). Higher scores on one-leg-stand were significantly related to a lower caries prevalence (logistic regression OR 0.81, 95%CI: 0.66–0.99, p = 0.037; Poisson regression exp(ß) 0.82, 95%CI: 0.74–0.91, p < 0.001). Coordination test under a time constraint (jumping side-to-side) showed no significant relation. Oral hygiene was poorer in younger children, boys and low SES. Caries prevalence increased with low SES and increasing age. The present results suggest that oral health is influenced by coordinative skills
Work Ability Mediates the Relationships between Personal Resources and Work Engagement
Research on job resources suggests strong links with work engagement, but less is known about its association with personal resources and possible mechanisms linking personal resources to work engagement. Based on the job demands-resources (JD-R) model and lifespan development theories, we develop and test a model of the indirect relationships between personal resources (i.e., adaptive coping in the form of selection, optimization, and compensation and personal health in the form of subjective health complaints) and work engagement through work ability. To test this model, a sample of employees (n = 520) was recruited from a panel of employed older (i.e., aged 40+) workers. Results suggest that work ability mediates the relationships between selection, optimization, and compensation and subjective health complaints and work engagement
Triage in Times of COVID-19: A Moral Dilemma
We present evidence from choice experiments on hypothetical triage decisions in a pandemic. Respondents have to decide who out of two patients gets ventilation. Patients are described in terms of attributes such as short-term survival chance, long-term life expectancy, and their current ventilation status. Attributes are derived from the ethical discourse among experts regarding triage guidelines during the COVID-19 pandemic and differ in the extent to which they are salient from a utilitarian or deontological perspective. Empirically, we find that although nonexperts agree with experts in prioritizing utilitarian attributes in triage decisions, nonexperts also consider the adherence to the norm of wearing face masks as particularly relevant. Furthermore, our study supports Greene and colleagues’ dual-process model of moral judgment; we find that utilitarian attributes are more decisive for respondents with a greater inclination toward utilitarianism and for respondents with a greater tendency toward reflection
Y-27632 Impairs Angiogenesis on Extra-Embryonic Vasculature in Post-Gastrulation Chick Embryos
Y-27632 inhibits Rho-associated coiled-coil-containing protein kinase (ROCK) signaling, which is involved in various embryonic developmental processes, including angiogenesis, by controlling actin cytoskeleton assembly and cell contractility. Administration of Y-27632 impairs cytoskeletal arrangements in post-gastrulation chick embryos, leading to ventral body wall defects (VBWDs). Impaired angiogenesis has been hypothesized to contribute to VBWDs. ROCK is essential in transmitting signals downstream of vascular endothelial growth factor (VEGF). VEGF-mediated angiogenesis induces gene expressions and alterations of the actin cytoskeleton upon binding to VEGF receptors (VEGFRs). The aim of this study was to investigate effects of Y-27632 on angiogenesis in post-gastrulation chick embryos during early embryogenesis. After 60 h incubation, embryos in shell-less culture were treated with Y-27632 or vehicle for controls. Y-27632-treated embryos showed reduced extra-embryonic blood vessel formation with impaired circulation of the yolk sac, confirmed by fractal analysis. Western blot confirmed impaired ROCK downstream signaling by decreased expression of phosphorylated myosin light chain. Interestingly, RT-PCR demonstrated increased gene expression of VEGF and VEGFR-2 1 h post-treatment. Protein levels of VEGF were higher in Y-27632-treated embryos at 8 h following treatment, whereas no difference was seen in membranes. We hypothesize that administration of Y-27632 impairs vessel formation during angiogenesis, which may contribute to failure of VWB closure, causing VBWDs